The long term goal of this project is to determine the significant ultrastructural, biochemical and physiological mechanisms of corneal scar formation with regard to mechanical strength and opacity of this tissue. The results of this research will be helpful in future studies concerned with the possibilities of altering the healing process. The immediate goals of this project are divided into three main areas: ULTRASTRUCTURAL STUDIES will deal with (a) differences between anterior and posterior portions of the healing wound with respect to dimensions, quantity and dispersion of collagen fibrils, and their three dimensional arrangement into fibers using transmission and scanning electron microscopy; (b) remodelling of stromal elements with time. BIOCHEMICAL STUDIES are subdivided into two areas: I. COLLAGEN: These experiments will attempt to (a) determine which cell type(s) in healing corneal wounds are responsible for the synthesis of the glycosylated dihydroxylysinonorleucine crosslink in collagen after reduction of these crosslinks with sodium borotritide; and (b) measure hydroxylysine glycosides of collagen in nanomole quantities using high voltage electrophoresis and fluorometric techniques. II. GLYCOSAMINOAGLYCANS research will involve: (a) further qualitative analyses of these macromolecules using enzymatic methods; (b) pharmacological attempts to modify glycosaminoglycan synthesis in corneal cells in vitro using UDP-xylose; and (c) enzymological studies of UDP-glucose dehydrogenase by characterizing the kinetic properties of this enzyme in scar tissue. PHYSIOLOGICAL STUDIES will be made to determine if nerve fibers innervate healing corneal tissue. Histochemical techniques will be used. These would be followed by studies on the effect of denervation on corneal would healing using chemical and/or physical means of denervating and assessing the healing process by quantitative parameters.